ヒトウロテンシンIIは,孤児受容体GPR14の強力な血管収縮剤およびアゴニストです
R S Ames1, H M Sarau, J K Chambers
1Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. bobvames1@sbphrd.com
Nature
|September 28, 1999
まとめ
強力な血管収縮剤であるウロテンシンII (U-II) は,心臓血管組織における新たに特定されたGタンパク質結合受容体 (GPR14) に結合する. このペプチドは血圧を大幅に上昇させ,心臓の機能を低下させ,より広範な生理学的役割を示唆します.
科学分野:
- 心血管薬理学について
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
背景:
- ウロテンシンII (U-II) は,ソマトスタチンのようなサイクルペプチドで,もともと魚から分離されました.
- 人間のU-IIとその受容体 (GPR14) は最近特定され,主に心血管組織で発現している.
研究 の 目的:
- ウロテンシンII.のヒト受容体を特定し,特徴づけること.
- 人間のU-IIが心血管系に及ぼす生理学的影響を調査する.
主な方法:
- ヒトのGタンパク質結合受容体 (GPR14) が,ネズミのGPR14に同類であることを確認した.
- リコンビナントヒトGPR14とGOBY/ヒトU-II.II.との結合測定法.
- カルシウム動員を測定する機能的測定法.
- 非ヒトの霊長類から分離された動脈に関するex vivo研究.
- 麻酔を受けた非ヒト霊長類の体内研究.
主要な成果:
- 人間のGタンパク質結合受容体 (GPR14) が特定され,U-II受容体であると確認されました.
- 人間のU-IIは,GPR14に高 afinityで結合し,カルシウム動員を誘発する.
- 人間のU-IIは,冠動脈動脈瘤を含む血管および心臓組織に存在します.
- U-IIは強力な血管圧縮剤であり,エンドセリン-1よりもはるかに強力です.
- In vivoでは,U-IIは外周抵抗性を高め,霊長類の心臓機能不全を引き起こした.
- U-II免疫反応は,中枢神経系および内分泌組織でも検出されました.
結論:
- 人間のU-IIは,心血管で発現する受容体であるGPR14を介して作用する.
- 人間のU-IIは,これまでに確認された哺乳類における最も強力な血管圧縮剤である.
- U-IIは,血管調節と心臓機能の調節に重要な役割を果たし,他のシステムでの潜在的な役割があります.
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